Progress in xenotransplantation following the introduction of gene-knockout technology.

Progress in xenotransplantation following the introduction of gene-knockout technology. Research Abstract Details 

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Progress in xenotransplantation following the introduction of gene-knockout technology. Abstract Text:

Hao-Chih Tai,Mohamed Ezzelarab,Hidetaka Hara,David Ayares,David K C Cooper,

The production of alpha1,3-galactosyltransferase gene-knockout (GT-KO) pigs has overcome the barrier of preformed anti-Galalpha1,3Gal (Gal) antibodies that has inhibited progress in pig-to-primate organ xenotransplantation for many years. Survival of GT-KO pig organs in nonhuman primates is currently limited by the development of a thrombotic microangiopathy that results in increasing ischemic injury of the transplanted organ over weeks or months. Potential causative factors include vascular endothelial activation from preformed anti-nonGal antibodies or cells of the innate immune system that recognize nonGal pig antigens directly, and coagulation dysregulation associated with molecular incompatibilities between pig and primate. Carefully isolated pancreatic islets from wild-type (genetically unmodified) adult pigs express minimal Gal epitopes, allowing survival sometimes for weeks or months after transplantation into nonhuman primates receiving immunosuppression directed only at T-cell function. However, there is a considerable immediate loss of islets, probably related to activation of coagulation and complement cascades. Further genetic manipulation of organ-source pigs is therefore required to overcome these problems. GT-KO pigs expressing a human complement-regulatory protein, e.g. decay-accelerating factor, and/or an 'anti-coagulant' gene, e.g. human tissue factor pathway inhibitor, might prevent the change in vascular endothelium from an anti-coagulant to a procoagulant phenotype, and protect the islets from early loss.

Progress in xenotransplantation following the introduction of gene-knockout technology. Publishing Authors By Initials

HC Tai,M Ezzelarab,H Hara,D Ayares,DK Cooper,

For similar surgical procedures, operative: transplantation: transplantation, heterologous research abstracts see: surgical procedures, operative: transplantation: transplantation, heterologous research

PUBMED ID PMID:

MEDLINE DATE:

Progress in xenotransplantation following the introduction of gene-knockout technology. Journal Published:

PUBLICATION TYPE: Review

Journal: Transplant international : official journal of the

VOLUME: 20

Page Numbers: 107-17

Journal Abbreviation: Transpl. Int.

ISSN: 0934-0874

DAY: 3

MONTH: Feb

YEAR: 2007

Progress in xenotransplantation following the introduction of gene-knockout technology. Information

Number of References: 89

LANGUAGE: eng

NlmUniqueID: 8908516

Progress in xenotransplantation following the introduction of gene-knockout technology. Keywords Mesh Terms:

KEYWORDS: Transplantation, Heterologous

MESH TERMS: immunology

Chemical & Substance for Abstract: Progress in xenotransplantation following the introduction of gene-knockout technology. Information

Substance Name: Galactosyltransferases

Registry Number: EC 2.4.1.-

Grant and Affiliation Information for Progress in xenotransplantation following the introduction of gene-knockout technology.

AFFILIATION: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.

Country: Germany

AGENCY: United States NIAID

GRANT: U01 AI068642

ACRONYM: AI

MEDLINETA: Transpl Int

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